title: Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein.
abstract: MutT-related proteins, including Escherichia coli MutT and the human MTH1 (NUDT1), degrade 8-oxo-7, 8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and thereby prevent mutations caused by the misincorporation of 8-oxoguanine into DNA. The human NUDT5, which has an intrinsic activity to cleave ADP sugars to AMP and sugar phosphate, possesses the ability to degrade 8-oxo-dGDP to the monophosphate. Since 8-oxo-dGDP and 8-oxo-dGTP are interconvertible by cellular enzymes, NUDT5 has the potential to prevent errors during DNA replication. The two activities associated with NUDT5 exhibit different pH dependencies; the optimum for the cleavage of ADP ribose is pH 7-9, while that for 8-oxo-dGDPase is around pH 10. The kinetic parameters for the two types of reactions indicated that ADP ribose is a better substrate for NUDT5 compared with oxidized guanine nucleotides. The 8-oxo-dGDP cleavage was competitively inhibited by ADP ribose and its reaction product, AMP, and in reverse, the cleavage of ADP ribose was inhibited by 8-oxo-dGDP. These results imply that the two types of substrates may share the same binding site for catalysis.
authors.affiliation: Department of Functional Bioscience and Advanced Science Research Center, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, Japan. itor1@college.fdcnet.ac.jp
authors.forename: Riyoko
authors.initials: R
authors.lastname: Ito
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Daiki
authors.initials: D
authors.lastname: Setoyama
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism*; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011755:Pyrophosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D009711:Nucleotides; D006147:Guanine; D000244:Adenosine Diphosphate; C403715:NUDT5 protein, human; D011755:Pyrophosphatases